Pharmacokinetics and stability of caldiamide sodium in rats
Okazaki, O.; Kurata, T.; Yoshioka, N.; Hakusui, H.
Arzneimittel-Forschung 46(1): 79-83
1996
ISSN/ISBN: 0004-4172 PMID: 8821523 Document Number: 467566
Gadodiamide (CAS 122795-43-1) injection (Omniscan) is a formulation composed of gadolinium (111) complexed with diethylenetriaminepentaacetic acid bis-methylamide (Gd DTPA-BMA) and the sodium calcium complex of the same ligand, known as caldiamide sodium (CAS 122760-91-2, NaCa DTPABMA), in a molar ratio of 20:1. Following intravenous dosing of NaCa DTPA-BMA (0.01 5 mmol/kg) in a 14C-labeled form, plasma concentrations of the drug declined rapidly with an elimination half-live of 0.31 h, a distribution volume of 244 ml/kg and a plasma clearance of 9.2 ml/min/kg. These results demonstrate that NaCa DTPA-BMA distributes into the extracellular fluid compartment and is renally excreted via glomerular filtration. Of the dose of radioactivity given, 86.6 % was excreted in urine by 4 h after injection, and 95.3 % in urine and 3.3 % in feces by 120 h. In addition, experiments were done to clarify the in vivo metabolism of NaCa DTPA-BMA. Results show small quantities of transchelatd forms of NaCa DTPA-BMA in urine. HPLC analysis demonstrated these metabolites were the Zn and Cu forms of the drug, resulting from displacement of the Ca ion in the NaCa DTPA-BMA molecule by endogeneous Zn or Cu. Further analyses by HPLC and ICP-AES demonstrate that the unchanged parent drug, the Zn and the Co forms occur in relative quantities of approximately 92%, 7%, and 1%, respectively. This demonstrates that the Ca ion in caldiamide sodium can be replaced by Zn or Cu ions in vivo, but only to a small extent.